Prognostic value of non-insulin-based insulin resistance indices in patients with newly diagnosed coronary artery disease: a cohort study
Aims : Insulin resistance (IR) plays a pivotal role in the onset and progression of coronary artery disease (CAD). This study aims to assess the efficacy and clinical utility of four non-insulin-based IR indices—Triglyceride-Glucose (TyG) index, Metabolic Score for Insulin Resistance (METS-IR), Triglyceride-Glucose-Body Mass Index (TyG-BMI), and Triglyceride to High-Density Lipoprotein Cholesterol ratio (TG/HDL-C)—in predicting prognosis in patients with newly diagnosed CAD. Methods This retrospective analysis included 890 patients with newly diagnosed CAD enrolled between January 2019 and June 2022. LASSO penalized regression was applied for covariate selection to mitigate overfitting (events-per-variable ratio ≈ 13.9), and Firth's penalized maximum likelihood estimation was performed as a sensitivity analysis. Multivariable Cox models and restricted cubic spline analyses examined associations between the four non-insulin-based IR indices and major adverse cardiovascular events (MACEs). The proportional hazards assumption was verified using Schoenfeld residual tests, and Bonferroni correction was applied for multiple comparisons (α = 0.0125). Receiver operating characteristic curves were plotted, and the incremental prognostic performance of each IR index for MACEs was assessed using the area under the ROC curve (AUC), C-statistics, net reclassification index (NRI), and integrated discrimination improvement (IDI). Kaplan–Meier analysis was used to evaluate the relationship between IR indices and clinical outcomes. Results Over a median follow-up of 26.5 months, the overall incidence of MACEs was 10.9%. TyG index (HR = 1.627, 95% CI: 1.228–2.145), TyG-BMI (HR = 1.019, 95% CI: 1.014–1.023), TG/HDL-C (HR = 1.127, 95% CI: 1.055–1.195), and METS-IR (HR = 1.104, 95% CI: 1.080–1.129) were all identified as independent risk factors for MACEs. METS-IR showed the highest incremental prognostic value (C-statistic = 0.779, IDI = 0.082, NRI = 0.356, P < 0.001). Log-rank tests indicated significantly higher MACEs rates in patients with higher IR indices (P < 0.01). Conclusions TyG index, TyG-BMI, TG/HDL-C ratio, and METS-IR are independently associated with MACEs in patients with newly diagnosed CAD, with METS-IR demonstrating the highest incremental predictive performance.